Chen Kunlun, Gao Qing, Zhang Wei, Liu Zhongwei, Cai Jiangyi, Liu Ying, Xu Jinkai, Li Jie, Yang Yi, Xu Xin
Department of General Surgery, Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
Liver Int. 2015 Mar;35(3):986-98. doi: 10.1111/liv.12458. Epub 2014 Jan 29.
BACKGROUND & AIMS: Musashi1 (MSI1) belongs to the RNA-binding protein (RBP) family, with functions as translational activator or suppressor of specifically bound mRNA. However, its function in hepatocellular carcinoma (HCC) has been deeply unexplored. Here, we investigated the role of MSI1 for proliferation and tumourigenesis in HCC.
The expression of MSI1 in HCC tissues was examined by immunohistochemistry and western blotting. The effects of MSI1 overexpression and silencing on cell proliferation, cell viability, tumoursphere and tumour formation of HCC were explored.
In this study, we initially reported that MSI1 was upregulated in HCC. Overexpression of MSI1 in HepG2 cell lines resulted in significantly promoted cell growth, tumour formation and cell cycle progression. Consistently, knockdown of MSI1 in Huh7 cell lines remarkably inhibited cell growth and tumour formation, and caused cell cycle arrest at the G1/S transition. Dual-luciferase assays indicated that MSI1 activated Wnt signal pathway, and APC and DKK1 were direct targets of MSI1.
Taken together, these findings indicate that an oncogenic role of MSI1 in HCC may be through modulation of cell growth and cell cycle by activating Wnt pathway via direct downregulation of APC and DKK1.
Musashi1（MSI1）属于RNA结合蛋白（RBP）家族，具有特异性结合mRNA的翻译激活或抑制功能。然而，其在肝细胞癌（HCC）中的作用尚未得到深入研究。在此，我们研究了MSI1在HCC增殖和肿瘤发生中的作用。
通过免疫组织化学和蛋白质印迹法检测HCC组织中MSI1的表达。探讨了MSI1过表达和沉默对HCC细胞增殖、细胞活力、肿瘤球形成和肿瘤形成的影响。
在本研究中，我们首次报道MSI1在HCC中上调。在HepG2细胞系中过表达MSI1导致细胞生长、肿瘤形成和细胞周期进程显著促进。同样，在Huh7细胞系中敲低MSI1显著抑制细胞生长和肿瘤形成，并导致细胞周期在G1/S期转换时停滞。双荧光素酶报告基因检测表明MSI1激活Wnt信号通路，APC和DKK1是MSI1的直接靶点。
综上所述，这些发现表明MSI1在HCC中的致癌作用可能是通过直接下调APC和DKK1激活Wnt通路来调节细胞生长和细胞周期。
